We sought to determine the relation of sex hormones with histologic pattern and severity in pediatric NAFLD. Methods: 73 children (<18 y) with biopsied NAFLD were evaluated in a cross-sectional prospective studyfrom the NASH CRN. Clinical data, sex hormone levels, and histologic features were compared between sexes. Hormones
were assayed using ELISA (androstenedione, DHEA-S, estradiol, estrone, leptin, SHBG, testosterone and adiponectin). Scored histology features included steatosis, inflammation and fibrosis as well as NAFLD patterns assessed by NASH CRN pathologists. Odds ratios and 95% CI’s were calculated between each sex hormone and histologic feature adjusted for sex, ethnicity and Tanner stage. Independent click here predictors of NASH diagnosis were determined from a stepwise multinomial logistic regression. Results: Subjects were 12.9 ± 2.6 yrs, 68% male, 52.1% Hispanic, average
BMI Z-score 2.3 ± 0.4 and Tanner stage 2.6 ±1.5. Overall, 37% had “NAFLD, No NASH, ” 14% see more had Zone 3 NASH, 22% had Zone 1 NASH and 27% had “Definite NASH”.32% had mild, 27% had moderate and 41% had severe steatosis. Sex hormones influenced NAFLD histology and patterning. Estradiol and estrone were significantly decreased in Zone 1 NASH vs. “NAFLD, No NASH” (Estradiol= 52.9土 15.5 vs.73.3土 30.8pg/mL, OR=0.62, p=0.01; Estrone= 40.38± 13.3 vs.61.9± 27.6 pg/mL, OR=0.58, p=0.007). Estrogen precursors were higher in mild steatosis as compared to moderate/severe (Estradiol= 66.3± 23.9 vs.64.5± 22.7pg/mL, OR=1.28, p=0.11; Estrone= 54.1± 24.9 vs.50.8± 23.7pg/mL, OR=1.24, Glutamate dehydrogenase p=0.14). Androstene-dione was decreased significantly in Zone 1 NASH vs. “NAFLD, No NASH” (1.01± 0.8 vs.1.2± 0.9ng/mL, OR=0.28, p=0.03). Adiponectin was significantly decreased in subjects with Definite NASH vs. “NAFLD, No NASH” (6467土 2834 vs.8676土 4461ng/mL; OR=0.80, p=0.04). Adiponectin and SHBG were decreased in moderate/severe vs. mild steatosis (8049±3354 vs.9862± 4630ng/mL, OR=0.85, p=0.02; 18.9± 9.4 vs.35, 4±
50.1nmol/L, OR 0.91, p = 0.004). Independent predictors of NASH diagnosis were gender, Tanner stage, DHEA-S, estrone, AST and GGT. Conclusions: Sex hormones associate with various aspects of NAFLD histology and patterning and may explain gender differences in NAFLD prevalence, histologic pattern and severity. We speculate these hormones signal through trans-activating mediators of lipid metabolism and inflammation. These clinically significant results warrant validation in larger cohorts. Disclosures: Joel E. Lavine – Consulting: Merck, Crosscare; Grant/Research Support: Janssen Cynthia A. Behling – Grant/Research Support: NASH CRN The following people have nothing to disclose: Elana B. Mitchel, Kathleen Viveiros, Katherine P. Yates, Janis Durelle, Jeffrey B. Schwimmer, Aynur Unalp Arida Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is recognized as an important health concern.